This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The association between CD4+ T-cell depletion and an accelerated rate of disease progression is well established for HIV infection in humans and simian immunodeficiency virus (SIV) infection in macaques. Prior to our studies, SIV infection in its natural primate host (i.e. sooty mangabeys) was observed to result in near normal levels of CD4+ T-cells despite similar plasma viral loads. Following transfer of plasma from an SIV+ mangabeys in 2000, and 2006, five mangabeys exhibited a decline in CD4+ T cell levels to below 100 cells/ul of blood which is also be observed in lymph nodes. These levels have remained between 18 and 100 cells/ul of blood for the past 9 years. The presence of what should be AIDS defining CD4+ T-cell levels in SIV+ mangabeys is an uncommon occurrence within the Yerkes colony (only four of the 105 SIV+ mangabeys screened are CD4-low). We recently tested the ability of these five (5) CD4-low SIV+ mangabeys to respond to an influenza vaccination. We vaccinated them twice and sent the plasma to the CDC for analysis to quantify the levels of influenza specific antibodies. Through microneutralization assays and hemaglutination inhibition it was determined that all five mangabeys were able to mount effective antibody responses to the influenza vaccination, even with the very low levels of CD4+ T cells. We are now assessing the various T cell subsets in these mangabeys to determine which of these subsets could potentially be fulfilling the T helper cell role in these SIV+ CD4-low mangabeys. Efforts thus far have identified the CD3+/CD4-/CD8- (double-negative) T cells as the most likely candidate.